Article of manufacture for the photodynamic therapy of dermal lesion

ABSTRACT

An article of manufacture for photodynamic therapy of a dermal lesion located at a dermal treatment site on skin including the stratum corneum, transparent hydrogel for covering the dermal treatment site and containing hydration agent and photopharmaceutical, the transparent hydrogel couples the hydration agent to the stratum corneum to hydrate and soften the stratum corneum to enhance its optical transmissiveness to facilitate the transmission of light therethrough and to enhance its chemical transmissiveness to facilitate the transmission therethrough of the photopharmaceutical for treatment of the dermal lesion; and light delivery means are included for delivering light through the transparent hydrogel and the hydrated stratum corneum to photoactivate the photopharmaceutical to treat the dermal lesion.

BACKGROUND OF THE INVENTION

This invention relates generally to an article of manufacture for thephotodynamic therapy (PDT) of dermal lesion such as for example actinickeratosis, basal carcinoma and psoriasis. More particularly, thisinvention relates to an article of manufacture for applying photodynamictherapy to a dermal lesion and which article of manufacture includes atransparent transport system containing hydration agent andphotopharmaceutical and light delivery means for photoactivating thephotopharmaceutical; the hydration agent hydrates primarily the corneumstratum of the epidermis to render the corneum stratum more transparentto the passage of light and the photopharmaceutical therethrough.

Bodies, sheet or layer forms, of hydrogel or hydrogel materials,particularly transparent (to light) hydrogels or hydrogel materials, arewell known in the medical field and may comprise, for example, apolyvinyl alcohol with a water matrix; some of these transparenthydrogels are castable gels or materials. They have been widely adaptedto such applications as diagnostic electrodes (for EKG), wound caredressings, and transdermal delivery devices for systemic delivery ofpharmaceutical agents. The biocompatability of this class of materialsis well established for extended contact with dermal structures. Much ofthe prior art in medical applications for hydrogel or hydrogel materialsteaches devices and methods for electrical conductivity enhancement.Critical in using hydrogel in many medical applications, such as anelectrical interface, is the ability of the hydrogel to form intimatephysical contact with skin or dermal structures. U.S. Pat. 5,143,071issued to Keusch et al. on Sep. 1, 1992, cites an extensive list anddescription of prior art hydrogels suitable for this purpose, and thispatent is incorporated herein by reference.

A concurrent body of prior art embraces hydrogels or hydrocolloids, aswound dressings and dressings impregnated with pharmaceutical compounds;representative of this prior art is U.S. Pat. 5,156,601 to Lorenze etal. Further, the work of Gombotz et al., Proc. Intl. Symp. Cont. Rel.Bioact. Mtl., Vol. 19, 1992, describes the rapid release of complexcompounds from hydrogels to skin or dermal structures.

U.S. Pat. No. 5,079,262 issued to Kennedy et al. discloses a method ofdetection and treatment of malignant and non-malignant lesions utilizing5-aminolevulinic acid. The acid is administered to a patient in anamount sufficient to induce synthesis of protoporphyrin IX in thelesions, followed by exposure of the treated lesions to aphotoactivating light in the range 350-640 nm. The acid is administeredto the patient orally, topically or by injection, but not through ahydrogel coupling; this patent is incorporated herein by reference.

None of the prior art references teach or suggest the photodynamictherapy of dermal lesions using transparent hydrogel as a coupling agentfor light and photopharmaceutical. Since its first reported clinical useat the turn of the century, photodynamic therapy has been accomplishedusing light projected to the dermal treatment site from sources at somedistance from the site. Modern photodynamic therapy (from 1978 onwards)has developed light delivery protocols using artificial sources such astungsten halogen, or xenon arc lamps with wavelength filtration toactivate photopharmaceuticals. All of the above light sources have beenused in projective, field illuminating devices that flood the targettreatment field or site in the treatment of superficial cutaneouslesions with light containing a wavelength designed to activate thephotopharmaceutical.

In the case of the tungsten and xenon-arc sources, extensive filtrationof the available light flux is essential to restrict the deliveredenergy to appropriate wavelengths that photoactivate thephotopharmaceutical in the target dermal structures. Colored glass orinterference filters used with these sources transmit some portion ofunwanted wavelengths, notably in the infrared region, and can causethermal effects that may mask the effect of photoactivity with anundesirable heating effect that also preferentially damages malignanttissue. High-power surgical lasers, even when de-focussed, also caninduce undesirable thermal effects. The work of Svaasland,Photochem/Photobiol. 1985, measured this effect and its impact on PDTprotocols.

Dosmerry of delivered photodynamically effective light to a dermaltreatment site is extremely difficult using current projective optics.Mathematical modeling of skin optics has been a slow and difficultprocess. Recent publications by Van Gemert et al., IEEE Trans. Biomed.Eng., Vol. 36;12, 1989, critically reviewed the prior work and presentsa 4-layer model of light-dermal tissue interaction; this publication isincorporated herein by reference Van Gemert et al. elaborates on theadvantages and effectiveness of the diffusion model of light transportin tissue, which depends upon the efficient coupling of the externallyapplied light to the target tissue. A later publication by R. RoxAnderson, Optics of the Skin, Clinical Photomedicine, DekkerPublication, 1993, reviews the two basic processes which govern theoptics or behavior of light in skin, namely, light absorption and lightscattering; this publication is incorporated herein by reference.

It has been found that an efficient and practical means of establishingthe diffusion conditions of light transport is to provide a transparentcoupling means that is in intimate contact with the dermal lesions onone surface and with the light source on its opposite surface. Underthese conditions reflective losses are reduced, and delivered energy ismuch more efficiently transmitted into the target region.

The stratum corneum present at a dermal treatment site on the skin of aperson is a formidable barrier to transport (transmission, penetrabilityor permeability) of light into the deeper structures of the skin wheredermal lesions typically reside, in whole or in part. The layeredplate-light corneocytes comprising the stratum corneum constitute anefficient reflective optical surface which reflects nearly all light inthe visible spectrum. There is some transmission in the region of 590 to700 nanometers. Photopharmaceuticals are formulated to be activated bylight energy in this region. Penetration depth is in the region of 1-3mm from the dry corneocyte surface. It has been discovered that theinterposition of a flexible transparent hydrogel coupling layer betweena monochromatic plate or sheet-formed light source and the skin surfaceconstitutes a new and more efficient delivery of activating opticalenergy to target dermal lesions for photodynamic therapy; particularlywhere the monochromatic light source delivers light at the specificwavelength at which the photopharmaceutical is photoactivated.

There are other substantial benefits that attend the use of anintimately contactive hydrogel coupling layer. Because hydrogels aretypically 60 to 90% water, hydration of the stratum corneum occursrapidly following contact with the hydrogel sheet. This hydration has asubstantial optical transparency, or optical transmissiveness, enhancingeffect, allowing more light to pass through the stratum corneum.Although the mechanism of this optical transparency has not beenextensively studied, it is thought to result from a reduction of thelight reflectivity of the stratum corneum through softening of thecorneocytes by a solvent or plasticizing action.

It is well established in the literature of chemical transport throughthe skin that hydration can enhance the chemical transparency,transmissiveness, passage or transport of pharmaceuticals through thestratum corneum. A review and discussion of this enhanced transportunder hydrated conditions is found in Ghosh et al., PharmaceuticalTech., Apr. 1993, which publication is incorporated herein by reference.

It follows that there are two key requirements of PDT to dermalstructures where the protocol requires topical application of thephotopharmaceutical. Transport of the photopharmaceutical into targettissue, and subsequent light activation of the photopharmaceutical atthe target tissue, these can be more efficiently accomplished using thediffusion route for both the drug and the activation optical energy.

It has been found that a transparent hydrogel coupling layer serves thedual purpose of establishing conditions for the optical energy diffusioninto skin tissue and photopharmaceutical compound diffusion or otherintroduction into skin tissue, by the intercellular or transcellularroutes; however, it will be understood that the introduction of thephotopharmaceutical from the hydrogel into the hydrated skin or throughthe hydrated stratum corneum, depending on the specificphotopharmaceutical used, can be by the above-noted diffusion, or byabsorption, or by other mechanism constituting chemical permeation orpenetration of the hydrated skin or stratum corneum. A third opticaladvantage of a transparent transport hydrogel is that it can remain inplace after PDT exposure, as a protective dressing.

It is an object of this invention to provide an article of manufacturefor the combined delivery of a photopharmaceutical and light forphotodynamic therapy of dermal lesions utilizing a transparent carrier,reservoir or transport of hydration agent and photopharmaceutical, andwhich transparent transport acts as an efficient coupler between a lightsource and dermal surface.

In the preferred embodiment of this invention, a transparent hydrogelserves as a transport or reservoir of a hydration agent andphotopharmaceutical and which hydrogel rapidly releases thephotopharmaceutical to the skin tissue. For purposes of photodynamictherapy, rapid delivery is desirable. This contrasts with prior arttransdermal devices for non-PDT drug delivery which seek to provide muchslower release kinetics for system absorption. Further, in the presentinvention, the photodynamic therapy is localized to a dermal treatmentsite defined by a cover, container or patch covering the site where thedermal lesion is located and the light necessary to activate thephotopharmaceutical is delivered only to the dermal treatment site. Itis thus advantageous to rapidly deliver the light activatedphotopharmaceutical doses to skin tissue, and dermal lesion, and thendeliver the light dose to initiate its biological activity to treat thedermal lesion.

The intimate transparent hydrogel contact established at the skinsurface of the treatment site forms both a fluid or fluidic coupling forthe photopharmaceutical and an optical or optic coupling for thephotoactivating light. In the case of the fluidic coupling, the watercontained in the hydrogel matrix begins to solubilize the stratumcorneum, hydrating this normally dry layer, and forms an avenue ofexchange between the hydrogel and the dermal lesion. Hydration enhancesboth intracellular and transcellular pathways. Upon establishment ofthese pathways, transport of the photopharmaceutical to target tissue ordermal lesion commences.

The effect of hydration on fluid transport across the stratum corneumlayer is substantial. Normally this structure contains 10-15% water.Hydrated stratum corneum can retain up to 50% water and the normal lightdiffusion coefficient of the hydrated stratum corneum can increaseten-fold.

The effect of hydration on optical coupling of light into skin tissue isalso substantial, but is sustainable only with the contact of thetransparent hydrogel to both the skin tissue and the light source. Inthe preferred embodiment a fiber optic panel comprising a plurality offiber optic strands is used as a light delivery source to activate thephotopharmaceutical, and hydrogel contact with the fiber optic strandsis efficient because at manufacture the hydrogel is cast against thefiber optic strands and conforms to the regular geometry of thesestrands. The formation of the hydrogel to skin surface juncture occursat the point of engagement of the hydrogel to the skin surface. Thephysical characteristics of the hydrogel necessary to establish intimateskin contact are those described for electrode contact in the prior artreferences, cited above. Similar characteristics are required forperforming PDT with the present invention, with the added hydrogelattributes of light transmission and hydration of the skin.

The mechanical changes hydration produces in the stratum corneum layerhave substantial impact on the optical coupling efficiency of externallyapplied light in the red region of the spectrum. The ultra-structure ofthe stratum corneum is an array of flattened essentially dead cellswhich are constantly being shed in a natural process of skin surfacerenewal. This results in a very uneven, dry, and highly light reflectivelayer or barrier to light penetration or transmission. Hydration bycontact with emollients and oil-based unguents confers an improvedsurface but the effect is transitory under projected opticalillumination schemes that, through surface heating, rapidly degrade thehydration effect by drying out of the target region. Thus thoughtopically applied agents for PDT may briefly induce an opticalimprovement, it rarely persists through the projected light illuminationphase if surface heating occurs during illumination.

This is in marked contrast with the present invention, where thehydrogel remains in place during the light dosage and serves as ahydration agent and photopharmaceutical reservoir or transport means,and conduit and coupling for both light and fluidized agents to thetarget tissue or dermal treatment site during all phases of photodynamictherapy of a dermal lesion.

SUMMARY OF THE INVENTION

An article of manufacture for photodynamic therapy of a dermal lesionlocated at a dermal treatment site on skin including the stratumcorneum, transparent coupling means for covering the dermal treatmentsite and which contains hydration agent and photopharmaceutical, thetransparent coupling means couples the hydration agent to the stratumcorneum at the dermal treatment site to hydrate and soften the stratumcorneum to enhance its optical transmissiveness to facilitate thetransmission of light therethrough and to enhance its chemicaltransmissiveness to facilitate the transmission therethrough of thephotopharmaceutical for treatment of the dermal lesion; and lightdelivery means for delivering light through the hydrated stratum corneumto photoactivate the photopharmaceutical to treat the dermal lesion.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatical illustration, substantially in cross-section,illustrating prior art photodynamic therapy of a dermal lesion usingprojection optics;

FIG. 2 is a diagrammatical illustration, substantially in cross-section,illustrating a first embodiment of an article of manufacture of thepresent invention;

FIG. 2A is a partial cross-sectional view of the cover of the article ofmanufacture of the present invention and which illustrates that theinternal surface of the cover may be provided with a suitable lightreflecting layer or coating;

FIG. 3 is a perspective cut away diagrammatical illustration of thefirst embodiment of an article of manufacture of the present inventionshown in situ over a dermal treatment site;

FIG. 3A is a partial perspective view of an optical fiber strandillustrating diagrammatically the lateral or radial exiting of laserlight;

FIG. 4 is an exploded view, partially in cross-section, illustrating asecond embodiment of an article of manufacture of the present invention;

FIG. 5 is a perspective diagrammatical illustration, substantially incross-section, illustrating the second embodiment of the article ofmanufacture of the present invention in situ over a dermal treatmentsite and also showing connection to a laser diode; and

FIG. 6 is a diagrammatical perspective view, partially in cross-section,illustrating a procedure tray containing the components of the firstembodiment article of manufacture of the present invention illustratedin FIGS. 2 and 3.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 illustrates prior art photodynamic therapy of dermal lesions 10located in a person's skin indicated by general numerical designation12, which skin includes the stratum corneum 14. [It will be understoodthat the dermal lesions 10 are illustrated diagrammatically in FIG. 1,and in FIGS. 2, 3 and 5 referred to below, by the darkest spots shown inthe skin 12. It will be further generally understood that the dermallesions 10 are generally located under the stratum corneum 14 or withinthe skin 12 or can extend partly outwardly of the skin as illustrated inFIG. 1.] Projective light source 13 directs light, indicated by arrows16, onto the skin 12 and, as noted generally above, the stratum corneum14 scatters the light with substantial portions of the light, asindicated by arrow 17, being reflected away from the stratum corneum 14and thereby not initiating any photodynamic therapy. However, as furthernoted above, red light within the light 16 can penetrate the skin 12 to3-4 mm. The projective light source 13 is typically either a filteredincandescent source or a laser and is normally arranged to project thelight 16 perpendicular to the skin 12 and corneum 14. It will be furtherunderstood from FIG. 1 that the dermal treatment site, indicatedgenerally by numerical designation 18, is generally not well defined indistinction to the dermal treatment site produced by the presentinvention described below and illustrated particularly in FIG. 2.

Referring to FIG. 2, the first embodiment of an article of manufactureembodying the present invention is indicated by general numericaldesignation 20. Article 20 includes a cover 22, which may be alsoreferred to as a container or patch, and may be made, for example, ofMylar and suitably formed into the shape shown such as for example byvacuum forming. It will be noted that the lower portion of the cover 22may be provided with an outwardly extending flange or peripheral portion23 circumscribing the lower cover portion, and which peripheral portion23 may be provided with a suitable layer of adhesive 24, of the typeknown to the art to be compatible with the human skin, for sealinglyengaging the skin 12 to seal the cover 22 to the skin and define andcover a dermal treatment site indicated by general numerical designation25; the flange or peripheral portion 23 and adhesive layer 24 are betterseen in FIG. 2A. It will be noted that in use of the article ofmanufacture 20 of the present invention illustrated in FIG. 2, thedermal treatment site 25 is comparatively narrowly and well defined ascontrasted to the open and comparatively poorly defined prior art dermaltreatment site 18 illustrated in FIG. 1. The cover 22 provides aninternal chamber 22A, better seen in FIG. 2A, opposite the dermaltreatment site 25 and a body or layer of transparent hydrogel 26 isreceived and resides within the chamber 25. Transparent hydrogel 26 maybe a transparent hydrogel of the type described above and may be, forexample, a polyvinyl alcohol having a water matrix which water serves asa hydration agent in the present invention; the water or hydration agentis illustrated diagrammatically in FIG. 2 by circles 27. In addition tocontaining the water or hydration agent 27, the transparent hydrogel 26includes a suitable photopharmaceutical for treating the dermal lesion10 and which photopharmaceutical is illustrated diagrammatically in FIG.2 by the circles 28; the photopharmaceutical 28 may be introduced intothe transparent hydrogel 26 by absorption. The photopharmaceutical 28may be, for example, photopharmaceutical 5-ALA available from the SigmaChemical Company, St. Louis, Mo., and which photopharmaceutical is madephotoactive by red light at a wavelength of substantially 635 nm.

The article of manufacture 20, FIG. 2, further includes a light deliverysource indicated by general numerical designation 30 and which may be anoptic laser light-emitting panel available from Lasermax, Inc., ofRochester, N.Y. which emits monochromatic red light having a wavelengthof substantially 635 nm so as to be photoactively compatible with andmatched to the photoactive wavelength of the photopharmaceutical 28contained in the transparent hydrogel 26. The optic laser light-emittingpanel 30 includes a plurality of optical fiber strands 31 indicated intransverse cross-section by the linearly aligned circles shown in FIG. 2and which strands 31 may be better seen in cylindrical perspective viewin FIG. 3. Referring to FIG. 2A, the cover 22 includes an internalsurface 34 which may be provided with a suitable layer or coating ofreflective material 35 which may be a layer of suitable reflective foilsuitably adhesed to the internal surface 34, or thermally stakedthereto, or may be a suitable reflective coating provided by a suitabledeposition process; reflective layer 35 is not shown in FIG. 2 since itis relatively thin as compared to the cover 22 but it will be understoodthat such reflective layer is present in article 20 of FIG. 2. The opticlaser light-emitting panel 30 resides within the chamber 25 and may besuitably secured to the cover 22, and to or through the reflective layer35, by a suitable adhesive or by suitable thermal staking. Thetransparent hydrogel 26 is castable and is cast into intimate physicaland optical contact with the optical fiber strands 31.

Referring to FIG. 3, it will be understood that the strands of opticalfibers 31 of the optic laser light-emitting panel 30 are actually theends or end portions of the optical fibers contained in the opticalfiber bundle 36 which terminate in a suitable optical fiber connector37; as shown in FIG. 4, the cover 22 is provided with a suitably sizedopening 51 for admitting the optical fiber bundle 36 therethrough.Connector 37 is for being connected to a suitable laser diode 40 forproducing, in the preferred embodiment, monochromatic red lightindicated by the arrows 42 having a wavelength of substantially 635 nm;the laser diode 36 may be, for example, a told 635 available fromToshiba Optical Systems. The laser light 42 is transmitted or ducted tothe optical strands 31, through the optical bundle 36 and, as may beunderstood from FIG. 3A, the optical fiber strands 31 are provided withside openings or lateral notches 39 which cause or permit the laserlight 42 (FIG. 3) to be emitted at a number of angles from the sides ofthe strands 31 but which light is ultimately reflected by the reflectivelayer or surface 35 (FIG. 2A) and caused to ultimately impinge upon thestratum corneum 15 and skin 12. As may be noted in FIG. 2, the laserlight, as indicated by the arrows 29, is reflected off the reflectivesurface (FIG. 2A) and transmitted through the transparent hydrogel 26.

Upon the article of manufacture 20, FIGS. 2 and 3, being sealinglyengaged to the skin 12 and stratum corneum 14 as illustrated in FIGS. 2and 3 and described above, the water or hydration agent 27 contained inthe transparent hydrogel 26 engages the stratum corneum 14 andimmediately begins to hydrate and soften the stratum corneum to enhanceits optical transparency or transmissiveness to facilitate thetransmission of the laser light 29 therethrough and to enhance itschemical transparency or transmissiveness to facilitate the transmissiontherethrough of the photopharmaceutical 28 and into the dermal treatmentsite 25 containing the dermal lesion 10. The laser light 42 (FIG. 3) isintroduced into the dermal treatment site 25 and illuminates the site bylight diffusion which photoactivates the photopharmaceutical 28 toinitiate its biological activity and to cause the photoactivatedphotopharmaceutical to biologically engage and treat the dermal lesion10. After such treatment, as noted generally above, the cover 22 of thearticle 20 may remain in place after the photodynamic therapy as atemporary protective dressing for the dermal treatment site 25. It willbe further understood that a biologically sufficient quantity ofphotopharmaceutical is introduced into the hydrogel to accomplishtreatment of the dermal lesion.

Referring now to FIGS. 4 and 5, a second embodiment of an article ofmanufacture of the present invention is shown and indicated by generalnumerical designation 20A. The structural elements in article 20A whichare the same, or substantially the same, as the corresponding structuralelements in article 20 of FIGS. 2 and 3, are given the same numericaldesignation as the elements in FIGS. 2 and 3. It will be generallyunderstood that article 20A applies photodynamic therapy to dermallesions 10, FIG. 5, in substantially the same manner as article 20 ofFIGS. 2 and 3. However, in the embodiment 20A, the transparent hydrogel26A while including the water or hydrating agent indicated by circles 27in FIG. 2, does not contain the photopharmaceutical indicated by circles28 in FIG. 2. Article 20A further includes a second layer or sheet oftransparent hydrogel 50 which is smaller in size or thickness thantransparent hydrogel 26A and which, although containing a water matrixin which the photopharmaceutical is contained, is highly dehydrated ascompared to the transparent hydrogel 26A. The relatively highlydehydrated state of the transparent hydrogel 50 permits the transparenthydrogel 50 to be cut and trimmed, such as by a pair of scissors 51,into a body of hydrogel 54 having a size much smaller than thetransparent hydrogel 26A and shaped into substantially the same shape asthe underlying dermal lesion 10, FIG. 5. As is known, thephotopharmaceutical contained in the transparent hydrogel 50 is toxic,typically acidic, and its application to the skin of a patient can be atleast somewhat painful. It has been discovered that by reducing the sizeof the hydrogel containing the photopharmaceutical a reduced but stillbiologically sufficient quantity of photopharmaceutical can be appliedphotodynamically to the patient but with reduced discomfort. This alsofacilitates a photopharmaceutical profile that minimizes the applicationof the photopharmaceutical to healthy tissue at the dermal treatmentsite 25, FIG. 5, yet allows the controlled delivery of photoactivatinglight to the entire dermal treatment site 25. In application, and inpractice of the photodynamic therapy, the trimmed hydrogel 54 resideswithin the cover 22 intermediate the transparent hydrogel 26A and thetreatment site 25 as may be noted particularly from FIG. 5. Thetransparent hydrogel 26A and trimmed hydrogel body 54 function insubstantially the same manner as the single layer of transparenthydrogel 26 in article 20 of FIGS. 2 and 3 to apply photodynamic therapyto the dermal lesion 10.

A procedure tray is indicated by general numerical designation 60.Procedure tray 60 is a single use procedure tray and may be suitablythermoformed from a suitable plastic such as polypropylene; the articles20 and 20A of the present invention, in the preferred embodiment, arealso single use articles. The tray is compartmentalized, as shown, toreceive, for example, the components or elements comprising the articleof manufacture 20 shown in FIGS. 2 and 3. The transparent hydrogel 26may be received within a moisture impervious foil or laminate pouch 61,the cover 22 and optic laser light emitting panel 30 may be received incompartments as shown also. The procedure tray 60 is sealed againstmoisture variation by a "peelable" foil sealing panel 63. The sealingpanel 28 is removed and the elements or components of the article ofmanufacture 20 are assembled as illustrated in FIGS. 2 and 3 andthereafter may be applied to the skin as described above and illustrateddiagrammatically in FIGS. 2 and 3.

It will be understood that the term photopharmaceutical as used hereinand in the appended claims means an agent which is itself aphotosensitizer or which is converted to a photosensitizer in the body.

It will be understood that many variations and modifications may be madein the present invention without departing from the spirit and the scopethereof.

What is claimed is:
 1. An article of manufacture for photodynamictherapy of a dermal lesion located at a dermal treatment site on skinwhich skin includes the stratum corneum, comprising:cover means adaptedfor being sealed to the skin for covering and defining a dermaltreatment site and for providing a chamber opposite the dermal treatmentsite; transparent transport means containing hydration agent and atleast one photopharmaceutical, said transport means residing in saidchamber and for engaging the skin at the treatment site to cause saidhydration agent to hydrate the stratum corneum at the dermal treatmentsite to enhance the passage therethrough of light and saidphotopharmaceutical; and light delivery means mounted to and inside saidcover and residing in said chamber for photoactivating saidphotopharmaceutical at said dermal treatment site to cause saidphotopharmaceutical to treat the dermal lesion.
 2. The article accordingto claim 1 wherein said transparent transport means comprise transparenthydrogel including a water matrix comprising said hydration agent. 3.The article according to claim 1 wherein said light delivery meanscomprise a fiber optic laser light emitting panel comprising a pluralityof optical fibers provided with side openings for the lateraltransmission of laser light therethrough to photoactivate saidphotopharmaceutical.
 4. The article according to claim 3 wherein saidcover means includes an internal surface defining said chamber andwherein said cover means further comprises a reflective layer providedon said internal surface for reflecting said laser light through saidtransparent hydrogel and to said photopharmaceutical.
 5. The articleaccording to claim 4, wherein said photopharmaceutical is photoactivatedat a predetermined wavelength and wherein said fiber optic laserlight-emitting panel provides monochromatic light at said predeterminedwavelength.
 6. The article according to claim 5 wherein saidpredetermined wavelength is 635 nm.
 7. The article according to claim 1wherein said cover means includes a lower portion provided with anoutwardly extending peripheral portion circumscribing said lower portionand a layer of adhesive applied to said peripheral portion for sealinglyengaging the skin to seal said cover means to the skin over said dermaltreatment site.
 8. The article according to claim 1 wherein saidtransport means comprise a first layer of transparent hydrogel receivedin said chamber and a second layer of transparent hydrogel received insaid chamber and for residing intermediate said first layer of hydrogeland the dermal treatment site, said first layer of hydrogel including awater matrix providing said hydration agent and said second layer ofhydrogel being smaller in size than said first layer and generallyshaped to cover only the dermal lesion located at the dermal treatmentsite, and said second layer of hydrogel including a water matrix intowhich said photopharmaceutical is absorbed.
 9. An article of manufacturefor photodynamic therapy of a dermal lesion located at a dermaltreatment site on skin which skin includes the stratum corneum,comprising:cover means adapted for being sealed to the skin for coveringand defining a dermal treatment site and for providing a chamberopposite the dermal treatment site; transparent coupling means containedin said chamber and for covering the dermal treatment site, saidtransparent coupling means containing at least one hydration agent andat least one photopharmaceutical, said transparent coupling means forcoupling said hydration agent to the stratum corneum at the dermaltreatment site to hydrate and soften the stratum corneum to enhance theoptical transmissiveness of the stratum corneum to facilitate thetransmission of light therethrough and to enhance its chemicaltransmissiveness to facilitate the transmission therethrough of saidphotopharmaceutical for treatment of the dermal lesion; and lightdelivery means mounted to and inside said cover and for delivering lightthrough said transparent coupling means and through said hydratedstratum corneum to illuminate the dermal treatment site by lightdiffusion to photoactivate said photopharmaceutical at said dermaltreatment site to treat the dermal lesion.